The endothelium is an important source of substances that cause contraction or relaxation of vascular smooth muscle. One of these substances is prostacyclin, or prostaglandin I2 (PGI2). PGI2 can relax vascular smooth muscle via an increase in cyclic adenosine monophosphate (cAMP;
Fig. 17.24 ). PGI2 is formed in the endothelium from muscle; its action is not endothelium mediated. Vasodilator agents such as adenosine, H+, CO2, and K+ may be released from parenchymal tissue and act locally on resistance vessels (see
Fig. 17.24
Lumen Endothelium Interstitial space Relaxation Basement membrane ATP ADP AMP Adenosine Parenchymal tissue cAMP RelaxationcGMP NO NP ACh GCyc L-arg. Vascular smooth muscle Cyc OxPGI2Syn PGI2 AA H+, CO2, K+
Injurytotheendotheliumofbloodvesselsprecedesatherosclerosis.Theprotective(antiatherogenic)effectoftheendotheliumresidesinseveralproperties.Forexample,theendotheliumregulatesadhesionofleukocytestothevesselwall,suppressestheproliferationofvascularsmoothmusclecells,maintainsavesselliningthatresiststheformationofthrombi,andregulatesvascularsmoothmuscletone.AllthesefunctionsinvolvetheactionofNO.Asindicatedpreviously,productionofNOisregulatedbymanysubstancesandbyshearstressactingonthevesselwall.
•Fig. 17.24 Endothelium-Mediated and Non–Endothelium-Mediated Vasodilation. Prostacyclin(PGI2)isformedfromarachidonicacid(AA)bytheactionofcyclooxygenase(CycOx)andprostacyclinsynthase(PGI2Syn)intheendotheliumandelicitsrelaxationoftheadjacentvascularsmoothmuscleviaincreasesincAMP.Stimulationoftheendothelialcellswithacetylcholine(ACh)orotheragents(seetext)resultsintheformationandreleaseofanendothelium-derivedrelaxingfactoridentifiedasnitricoxide(NO).NOstimulatesguanylylcyclase(GCyc)toincreasecGMPinthevascularsmoothmuscletoproducerelaxation.Thevasodilatornitroprusside(NP)actsdirectlyonvascularsmoothmuscle.Substancessuchasadenosine,H+ ,CO2,andK+ canariseintheparenchymaltissueandelicitvasodilationbydirectactiononvascularsmoothmuscle.ADP,adenosinediphosphate;AMP,adenosinemonophosphate;ATP,adenosinetriphosphate;cAMP,cyclicadenosinemonophosphate;cGMP,cyclicguanosinemonophosphate;L-arg,L-arginine.
arachidonic acid, and the process is catalyzed by PGI2 synthase. The mechanism that triggers synthesis of PGI2 is not known. However, PGI2 may be released by an increase in shear stress caused by accelerated blood flow. The primary function of PGI2 is to inhibit platelet adherence to the endothelium and platelet aggregation and thus prevent intravascular clot formation. PGI2 also causes relaxation of vascular smooth muscle.
Of far greater importance in endothelium-mediated vascular dilation is the formation and release of nitric oxide (NO), a component of endothelium-derived relaxing factor (see